PB2088: IMMUNE PROFILE OF PATIENTS WITH FOLLICULAR LYMPHOMA ASSESSED BY FLOW CYTOMETRY IN PERIPHERAL BLOOD: CHARACTERISTICS AT DIAGNOSIS AND AT RELAPSE OF THE DISEASE
Authors: A. Rivero Arango, P. Mozas, J. Correa, A. Rivas-Delgado, F. Araujo-Ayala, K. Guinetti, A. Bataller, M. Condom, A. Gaya, J. Delgado, E. Giné, P. Perez-Galán, E. Campo, A. Vlagea, E. Matutes, A. López-Guillermo, N. Villamor, L. Magnano
Journal: HemaSphere (2022)

Background: Follicular lymphoma (FL) is the indolent lymphoma more frequently diagnosed in Western countries and is characterized by a heterogeneous clinical course. The biologic importance of the tumour microenvironment in FL pathogenesis is well established. However, detailed information on the immune profile in peripheral blood (PB) has not been previously investigated. In the current era of CAR-T cell therapy and bispecific antibodies, the characterization of the immune cellular populations in the blood becomes very relevant. Aims: Characterize the immune populations in PB of patients with FL at diagnosis and at relapse, and compare them with healthy controls. In addition, a subanalysis was performed on the relapse group to identify associations between immune populations and POD24. Methods: We collected samples of FL patients either at diagnosis (n=35) or at relapse (n=34) from March 2019 to December 2021 (median age: 61 years [27-81]; 40M/29F). Sixteen of the 34 relapsed patients were POD24. Moreover, 15 PB samples from healthy donors were also obtained (median age: 31 years [28-65]; 5M/10F). Baseline characteristics of the FL patients were collected. All individuals signed informed consent to participate in the study. The identification of different immune populations (major subsets of T-cells, B-cells, NK cells, monocytes, neutrophils, eosinophils, basophils, dendritic cells and myeloid suppressor cells) was performed by multiparameter flow cytometry. Euroflow methodology was used to set up the Omnicyt cytometers. 150.000 events were the minimum acquired by the Omnicyt™ flow cytometer. All data were analysed using Infinicyt™ software version 2.0 (Cytognos, Salamanca Spain). The Mann-Whitney U test was used to compare means between FL patients and healthy controls, and the chi-squared test was used to assess the association of immune populations with POD24. Immune populations were categorized using the mean percentage value of healthy controls as cut-off. Results: Detailed data of immune populations of FL patients and healthy controls is shown in the table. Compared with healthy controls, patients with FL showed a lower CD4+/CD8+ ratio due to an increase in CD8+ lymphocytes and a decrease in total CD4+ lymphocytes. In addition, FL patients had a significantly lower percentage of naive T lymphocytes, a higher percentage of effector memory and effector lymphocytes, both CD4+ and CD8+, and a higher percentage of activated CD4+ and CD8+ lymphocytes (p<0.0001 in all cases). Of note, FL PB samples had increased percentage of memory and activated regulatory T lymphocytes (Treg) (p= 0.01). These differences were maintained when immune populations were compared at diagnosis and at relapse (see table). Finally, patients with FL at diagnosis showed a decrease percentage of myeloid dendritic cells (p= 0.04). No differences were observed in the percentage of neutrophils, monocytes, eosinophils or total B lymphocytes. Interestingly, POD24 events were found in patients who had higher CD8+effector and/or lower CD8+ central memory percentages in comparison with no POD24 patients (p= 0.004). Image:Summary/Conclusion: FL patients show an immunological profile in PB that is significantly different from that observed in healthy controls. The high CD8+effector and/or low CD8+central memory profile is significantly associated with early relapse patients. Knowledge of these immune alterations may contribute to the understanding of its pathogenesis and behaviour and might help to devise new immunotherapeutic strategies adapted to the patient´s immunological profile.